Abstract
Aim To evaluate the impact of PIK3CA mutation status on clinical outcomes of HR+ breast cancer treated with PI3K inhibitors. Methods A comprehensive literature search was conducted in online databases from inception to December 31, 2019. The main characteristics and prognostic data of each eligible study were extracted. The odds ratio (OR) for the overall response rate (ORR) and hazard ratio (HR) for progression-free survival (PFS) were estimated using the fixed-effects Mantel-Haenszel model. Results A total of 8 studies involving 2670 patients were included for analysis. Overall, the clinical outcomes of PI3K inhibitors were significantly influenced by PIK3CA mutation status in HR+ breast cancer. After the treatment of PI3K inhibitors, HR+ breast cancer patients with PIK3CA mutations presented better ORR (PIK3CA-mutated group: OR = 1.98 [95% CI, 1.46 to 2.70]; PIK3CA wild-type group: OR = 1.09 [95% CI, 0.78 to 1.53]) and better PFS (PIK3CA-mutated group: HR = 0.65 [95% CI, 0.55 to 0.76]; PIK3CA wild-type group: HR = 0.87 [95% CI, 0.70 to 1.09]). No publication bias was detected for ORR and PFS in our analysis. Conclusion In this meta-analysis, it suggests that the association between clinical outcomes of PI3K inhibitors and PIK3CA mutation status is dramatic. PIK3CA mutations were a favorable factor in the clinical outcomes of HR+ breast cancer treated with PI3K inhibitors.
Highlights
Breast cancer is the most commonly diagnosed cancer in women worldwide
Pooled overall response rate (ORR) demonstrated that PI3K inhibitors generated 1.98 [95% CI, 1.46 to 2.70] odds ratio (OR) in hazard ratio (HR)+/ PIK3CA-mutated breast cancer patients and 1.09 [95% CI, 0.78 to 1.53] odds ratio (OR) in HR+/PIK3CA wild-type breast cancer patients
HR+/PIK3CA wild-type group (HR = 0:87 [95% CI, 0.70 to 1.09]), the progression-free survival (PFS) of PI3K inhibitors was further improved in the HR+/PIK3CA-mutated group (HR = 0:65 [95% CI, 0.55 to 0.76])
Summary
Breast cancer is the most commonly diagnosed cancer in women worldwide. More than 80% of breast cancer is classified as hormone receptor-positive (HR+) breast cancer [1]. Current therapeutic strategies for HR+ breast cancer comprise endocrine therapy, mTOR, or cyclin-dependent kinase 4/6 (CDK4/6) inhibition et al disease progression, metastasis, and drug resistance eventually develop [2]. To our knowledge, diversified pathways (e.g., RAS/MAPK, NFκB, or PI3K/AKT/mTOR) get involved in drug resistance to current therapy [3]. Monotherapy targeting a single pathway can be failed to generate clinical benefit due to the aberrant activation of bypass signaling. PI3K/AKT/mTOR is the most frequently altered pathway in
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